Landa Natali, Miller Liron, Feinberg Micha S, Holbova Radka, Shachar Michal, Freeman Inbar, Cohen Smadar, Leor Jonathan
Neufeld Cardiac Research Institute, Sheba Medical Center, Tel-Aviv University, Tel-Hashomer 52621, Israel.
Circulation. 2008 Mar 18;117(11):1388-96. doi: 10.1161/CIRCULATIONAHA.107.727420. Epub 2008 Mar 3.
Adverse cardiac remodeling and progression of heart failure after myocardial infarction are associated with excessive and continuous damage to the extracellular matrix. We hypothesized that injection of in situ-forming alginate hydrogel into recent and old infarcts would provide a temporary scaffold and attenuate adverse cardiac remodeling and dysfunction.
We developed a novel absorbable biomaterial composed of calcium-crosslinked alginate solution, which displays low viscosity and, after injection into the infarct, undergoes phase transition into hydrogel. To determine the outcome of the biomaterial after injection, calcium-crosslinked biotin-labeled alginate was injected into the infarct 7 days after anterior myocardial infarction in rat. Serial histology studies showed in situ formation of alginate hydrogel implant, which occupied up to 50% of the scar area. The biomaterial was replaced by connective tissue within 6 weeks. Serial echocardiography studies before and 60 days after injection showed that injection of alginate biomaterial into recent (7 days) infarct increased scar thickness and attenuated left ventricular systolic and diastolic dilatation and dysfunction. These beneficial effects were comparable and sometimes superior to those achieved by neonatal cardiomyocyte transplantation. Moreover, injection of alginate biomaterial into old myocardial infarction (60 days) increased scar thickness and improved systolic and diastolic dysfunction.
We show for the first time that injection of in situ-forming, bioabsorbable alginate hydrogel is an effective acellular strategy that prevents adverse cardiac remodeling and dysfunction in recent and old myocardial infarctions in rat.
心肌梗死后不良的心脏重塑和心力衰竭进展与细胞外基质的过度和持续损伤有关。我们推测，将原位形成的海藻酸盐水凝胶注入近期和陈旧性梗死灶可提供一个临时支架，并减轻不良的心脏重塑和功能障碍。
我们研发了一种新型可吸收生物材料，其由钙交联海藻酸钠溶液组成，该溶液具有低粘度，注入梗死灶后会发生相变形成水凝胶。为了确定注射后生物材料的效果，将钙交联生物素标记的海藻酸钠在大鼠前壁心肌梗死后7天注入梗死灶。系列组织学研究显示海藻酸盐水凝胶植入物原位形成，占据瘢痕面积的50%。生物材料在6周内被结缔组织替代。注射前及注射后60天的系列超声心动图研究显示，将海藻酸生物材料注入近期（7天）梗死灶可增加瘢痕厚度，减轻左心室收缩期和舒张期扩张及功能障碍。这些有益效果与新生心肌细胞移植相当，有时甚至更优。此外，将海藻酸生物材料注入陈旧性心肌梗死（60天）可增加瘢痕厚度并改善收缩期和舒张期功能障碍。
我们首次表明，注射原位形成的、可生物吸收的海藻酸盐水凝胶是一种有效的无细胞策略，可预防大鼠近期和陈旧性心肌梗死中的不良心脏重塑和功能障碍。
